대한신장학회

논문분류	춘계학술대회 초록집
제목	Single-Cell Transcriptomic and Clonal Profiling Reveals Shared Signatures of Gd-IgA1 Stratification and B-Cell Clonal Expansion in IgA Nephropathy
저자	Jinsun Lee
출판정보	2026; 2026(1):
키워드	IgA nephropathy, Galactose-deficient IgA1, Clonal expansion, Single-cell transcriptomics
초록	Objectives: Galactose-deficient IgA1 (Gd-IgA1) is central to the pathogenesis of IgA nephropathy (IgAN), but the immune-cell clonotypes involved in Gd-IgA1–related immune responses remain poorly characterized. We aimed to profile transcriptional changes across Gd-IgA1–stratified IgAN groups and assess their overlap with expanded immune-cell clones. Methods: Cells of interest were sorted with fluorescence-activated cell sorting. T follicular helper (Tfh) cells, activated B cells, and antibody-secreting cells (ASCs) from 12 IgAN patients and 6 healthy controls (HC) were profiled by 5′ single-cell RNA sequencing with paired V(D)J analysis. IgAN samples were stratified into low- and high-Gd-IgA1 groups (n=6 each). Differential expression (DE) analyses identified monotonic changes across HC, low-Gd-IgA1, and high-Gd-IgA1 groups and compared expanded (clone size ≥3) versus non-expanded clones within each cell type. Shared pathways between Gd-IgA1-associated monotonic DEGs and expanded clone-associated DEGs were then assessed. Results: In Tfh cells, pathways related to apoptosis, T-cell selection, and mRNA splicing showed monotonic decreases. Activated B cells showed monotonic decreases in mRNA splicing- and cell-cell adhesion-related pathways. In ASCs, intracellular trafficking-related pathways increased, whereas apoptosis-related pathways decreased monotonically. Clonal expansion was observed only in B-cell compartments, with no expanded clones detected in Tfh cells. The proportion of expanded clones increased across HC, low-Gd-IgA1, and high-Gd-IgA1 groups. Expanded clones in activated B cells were enriched for apoptosis- and mRNA splicing-related pathways, whereas expanded ASC clones showed decreased enrichment of antigen processing, mRNA splicing, and apoptosis-related pathways. In ASCs, both Gd-IgA1-associated and expanded clone-associated analyses showed decreased enrichment of apoptosis-related pathways. Conclusion: Cell type-specific transcriptional changes were observed across Gd-IgA1–stratified groups, with stepwise increases in expanded B-cell clones. In ASCs, decreased enrichment of apoptosis-related pathways was observed in both Gd-IgA1-associated and expanded clone-associated analyses. These findings suggest that B-cell clonal expansion may contribute to Gd-IgA1-associated immune responses in IgAN, particularly through shared apoptosis-related pathway alterations in ASCs.
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